Critical aspects in the process of gas exchange at the peripheral tissue level are still poorly understood. Quantitative data essential to the analysis of diffusion pathways, such as capillarity (O2 supply) in different muscles, and its relation to maximal O2 uptake, environmental O2 availability and O2 demand (muscle cells oxidative capacity) have been either missing or controversial. I propose to apply a method we recently developed to estimate the length density of anisotropic structures, capillaries in skeletal muscles to quantify the capillary network in muscles of animals with different O2 requirements and/or exposed to different environmental O2 availability, I will analyse animals 1) differing in O2 demand in normoxic conditions (terrestrial mammals of different size and performance; reptiles; birds), 2) exposed to acute and chronic hypoxia (rats given low O2 mixtures to breathe, and at high altitude), and 3) tolerant to extreme anoxia (diving marine mammals with different energy requirements; birds acclimated to higher altitude). The measurements of the capillary network will be correlated with the comparative analysis of the size of the mitochondrial compartment and fiber size in the same samples. Different skeletal muscles (mostly aerobic, glycolytic and mixed muscles), and the heart (correlation with work rate) will be analysed in each animal group. My specific aims are to determine: 1) structure-function relationships in the design of the respiratory system from mitochondria in muscles (main site of O2 consumption), over muscle fiber size (O2 diffusion pathways), to muscle capillaries (O2 supply) in the heart and skeletal muscles in different animal models, and 2) to evaluate which adaptative changes can occur (or not) in the design of the respiratory system of peripheral tissue in response to limited environmental O2. This will provide new insights in the understanding of structure-function correlations in tissue gas exchange, and possibly help in the understanding of human response to hypoxemia.